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At least 19 records

A Biodosimeter for Multiparametric Determination of Radiation Dose, Radiation Quality, and Radiation Risk

Predicting risk of human cancer following exposure of an individual or a population to ionizing radiation is challenging. To an approximation, this is because uncertainties of uniform absorption of dose and the uniform processing of dose-related damage at the cellular level within a complex set of biological variables degrade the confidence of predicting the delayed expression of cancer as a relatively rare event. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the risk of developing cancer by the cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported. This is the demonstration of a dose responsive field effect of enhanced expression of keratin 18 (K18) in cultures of human mammary epithelial cells irradiated with cesium-1 37 gamma-rays. Dose response of enhanced K18 expression was experimentally extended over a range of 30 to 90 cGy for cells evaluated at mid-log phase. K18 has been reported to be a marker for tumor staging and for apoptosis, and thereby serves as an example of a potential marker for cancer risk, where the reality of such predictive value would require additional experimental development. Since observed radiogenic increase in expression of K18 is a field effect, ie., chronically present in all cells of the irradiated population, it may be hypothesized that K18 expression in specific cells absorbing particulate irradiation, such as the high-LET-producing atomic nuclei of space radiation, will report on both the single-cell distributions of those particles amongst cells within the exposed population, and that the relatively high dose per cell delivered by densely ionizing tracks of those intersecting particles will lead to cell-specific high-expression levels of K18, thereby providing analytical end points that may be used to resolve both the quantity and the quality of the radiation dose absorbed by individual cells. The principal value of this reported potential multiparametric cellular biodosimeter is suggested to be that it justifies a search for similar but more robust radiogenic assays. That is, K18 is only one radiation dose-sensitive expressed protein, whereas analytical techniques of genomics and proteomics can be used to simultaneously analyze multiple gene and protein expressions resulting from radiation-dose absorption. The potential usefulness of multiparametric cellular biodosimeters will be best realized from quantitatively profiling these multiple markers using these modern techniques.

Richmond, Robert↗

Relationship Between Radiation Dose and Markers of Insulin Resistance and Inflammation in Atomic Bomb Survivors

Abstract Context In recent studies of childhood cancer survivors, diabetes has been considered a late effect associated with high therapeutic doses of radiation therapy. Our recent study of atomic bomb (A-bomb) survivors also suggested an association between radiation dose and diabetes incidence, with exposure city and age at exposure as radiation dose effect modifiers. Insulin resistance mediated by systemic inflammation and abnormal body composition has been suggested as a possible primary mechanism for the incidence of diabetes after total body irradiation; however, no studies have examined low to moderate radiation exposure (<4 Gy) and insulin resistance in A-bomb survivors. Objective To examine the association between radiation dose and markers of inflammation and insulin resistance. Methods This study investigated 3152 survivors who underwent a health examination between 2008 and 2012 and who were younger than 15 years at exposure. Multivariate linear regression analyses were used to evaluate the radiation effects on levels of markers of inflammation and insulin resistance. Results Radiation dose was significantly and positively associated with levels of C-reactive protein, triglycerides, homeostasis model assessment of β-cell function (HOMA-β), and HOMA of insulin resistance (HOMA-IR) after adjustment for relevant covariates including sex, city, and age at exposure. Adiponectin and high-density lipoprotein cholesterol levels were also associated significantly and negatively with radiation dose. However, city was not a dose modifier of the radiation response on these markers of inflammation and insulin resistance. Conclusion Insulin resistance might be a possible factor in radiation-related diabetes incidence in A-bomb survivors.

Endocrinology & Metabolism↗

Effects of chronic low-dose radiation on cataract prevalence and characterization in wild boar (Sus scrofa) from Fukushima, Japan

This study evaluated cataracts in wild boar exposed to chronic low-dose radiation. We examined wild boar from within and outside the Fukushima Exclusion Zone for nuclear, cortical, and posterior subcapsular (PSC) cataracts in vivo and photographically. Plausible upper-bound, lifetime radiation dose for each boar was estimated from radioactivity levels in each animal’s home range combined with tissue concentrations of 134+137Cesium. Fifteen exposed and twenty control boar were evaluated. There were no significant differences in overall prevalence or score for cortical or PSC cataracts between exposed and control animals. Nuclear (centrally located) cataracts were significantly more prevalent in exposed boar (p<0.05) and had statistically higher median scores. Plausible upper-bound, lifetime radiation dose ranged from 1 to 1,600 mGy in exposed animals, with no correlation between dose and cortical or PSC score. While radiation dose and nuclear score were positively associated, the impact of age could not be completely separated from the relationship. Additionally, the clinical significance of even the highest scoring nuclear cataract was negligible. Based on the population sampled, wild boar in the Fukushima Exclusion Zone do not have a significantly higher prevalence or risk of cortical or PSC cataracts compared to control animals.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

Radiation-induced acute coronary events (ACEs) may occur as a treatment-related late adverse effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remain to be determined. The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in patients with BC treated with radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Microreactor Incident-Free Transportation Radiation Dose Assessment

This report, prepared by Pacific Northwest National Laboratory (PNNL) for the U.S. Nuclear Regulatory Commission, provides an estimate of the radiation dose related to the transportation of microreactors following the regulatory limits established in Title 10 of the Code of Federal Regulations (10 CFR) 71.47(b). The transportation of irradiated microreactors poses unique challenges. Microreactors may be challenged to meet the current 10 mrem/hr limit at 2 meters from the vehicle in 10 CFR 71.47(b). The need to modify packaging to be within practical weight and size limits for shipping may limit the amount of shielding that can be applied for a microreactor transportation package design. Operational strategies that would necessitate moving a reactor within a short time after its operating life may result in higher radiation dose rates associated with lower cooling times. This study estimates the radiation dose to maximally exposed individuals (MEIs) under the current regulatory radiation level limit of 10 mrem/hr at 2 meters from the vehicle as well as alternative limits of 10, 50, 100, and 200 mrem/hr at 2 meters from the vehicle. This analysis expands on prior incident free transportation radiation dose assessments conducted for spent nuclear fuel (SNF) and radioactive waste transportation. The key factors analyzed include the microreactor fuel type and burnup, shipment cooling periods, shielding designs integrated into transport packaging, and exposure scenarios for MEIs for highway and rail transport. This report considers additional distances that may be associated with compensatory measures to ensure safe transport conditions under varying radiation dose limits, including enhanced routing measures, escort protocols, vehicle inspections, and operational restrictions.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1.Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. We have completed infection studies of the 3-D biomimetic intestinal tissue models and are currently analyzing the data.

Jennifer Barrila↗

Effects of Low Dose Radiation and Radiation Countermeasures on Infection By Spaceflight Analogue Cultured Salmonella Using 3-D Biometric Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗

Effects of Low Dose Radiation and Radiation Countermeasures on Infection by Spaceflight Analogue Cultured Salmonella Using 3-D Biomimetic Human Tissue Models

While both microgravity and radiation are major biological stressors associated with the spaceflight environment, their cumulative impact on host-pathogen interactions and infectious disease risks are rarely considered. This is critical to address, since the cumulative effects of these stressors during spaceflight may result in unexpected negative impacts on crew health and performance that neither condition alone would predict, thus limiting the ability to develop effective countermeasures. Previously, we showed that both spaceflight and spaceflight analogue culture increased the virulence and pathogenesis-related characteristics of the foodborne pathogen, Salmonella Typhimurium (S. Typhimurium), which is responsible for disqualification of food destined for the International Space Station and Salmonella spp. have been found aboard NASA spacecraft. Recently, we demonstrated that spaceflight-analogue culture of S. Typhimurium increased its ability to infect 3-D biomimetic human intestinal tissue models. In a separate study, we showed low dose radiation damaged our 3-D intestinal models. The primary objective of this proposal is to evaluate the possibility that low dose radiation will exacerbate the already increased bacterial pathogenicity of S. Typhimurium observed following spaceflight analogue culture. In addition, we will determine the impact of a radiation countermeasure to provide protection against both radiation and pathogen-induced tissue damage and inflammation. Hypothesis: The already enhanced infection potential of spaceflight analogue cultured S. Typhimurium will be further exacerbated when used to infect host cells exposed to low dose radiation and this enhanced pathogenicity can be mitigated by a radioprotective compound. Aims: 1. Characterize the impact of spaceflight-analogue culture on the ability of S. Typhimurium to infect 3-D biomimetic intestinal tissue models before and after exposure to low dose radiation. 2. Evaluate the ability of the radioprotective compound, EC-18, to protect 3-D intestinal models from low dose radiation, S. Typhimurium infection, and the cumulative impact of these stressors. Significance: Current infectious disease risk assessments for spaceflight do not consider the potential for increased susceptibility to infection and disease resulting from exposure to low dose radiation, which is a critical consideration. This study will provide key evidence to determine if exposure to low dose radiation may be a factor in astronaut susceptibility to infection during long duration exploration missions and the impact of selected countermeasures to mitigate that risk to crew health. This study has been initiated and data collection is beginning.

Jennifer Barrila↗

Crew radiation dose from the plume of a high impulse gas-core nuclear rocket during a Mars mission.

Analytical calculations are performed to determine the radiation dose rate and total dose to the crew of a gas-core nuclear rocket from the fission fragments located throughout the plume volume. The radiation dose from the plume fission fragments to two crew locations of 100 and 200 meters from the nozzle exit are calculated. It is found that, in the case of the most probable fission fragment retention time of 100 seconds, the crew must be protected from the radiation dose. Five centimeters of lead shielding would reduce the radiation dose by two orders of magnitude thereby protecting the crew. The increase in vehicle weight would be insignificant (7150 kg to a vehicle gross weight of 0.94 million kg).

Masser, C. C.↗

Total-dose radiation effects data for semiconductor devices: 1985 supplement, volume 1

Steady-state, total-dose radiation test data are provided, in graphic format, for use by electronic designers and other personnel using semiconductor devices in a radiation environment. The data were generated by JPL for various NASA space programs. The document is in two volumes: Volume 1 provides data on diodes, bipolar transistors, field effect transistors, and miscellaneous semiconductor types, and Volume 2 provides total-dose radiation test data on integrated circuits. Volume 1 of this 1985 Supplement contains new total-dose radiation test data generated since the August 1, 1981 release date of the original Volume 1. Publication of Volume 2 of the 1985 Supplement will follow that of Volume 1 by approximately three months.

Martin, K. E.↗

Pneumonia After Bacterial or Viral Infection Preceded or Followed by Radiation Exposure: A Reanalysis of Older Radiobiologic Data and Implications for Low-Dose Radiation Therapy for Coronavirus Disease 2019 Pneumonia

Currently, there are about 15 ongoing clinical studies on low dose radiation therapy for Coronavirus Disease 2019 pneumonia. One of the underlying assumptions is that irradiation of 0.5 to 1.5 Gy is effective at ameliorating viral pneumonia. We aimed to reanalyze all available experimental radiobiologic data to assess evidence for such amelioration.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Conformal Avoidance of Normal Organs at Risk by Perfusion-Modulated Dose Sculpting in Tumor Single-Dose Radiation Therapy

Although 24 Gy single-dose radiation therapy (SDRT) renders >90% 5-year local relapse-free survival in human solid tumor lesions, SDRT delivery is not feasible in ∼50% of oligometastatic lesions owing to interference by dose/volume constraints of a serial organ at risk (OAR). Conformal OAR avoidance is based on a hypothetical model positing that the recently described SDRT biology specifically permits volumetric subdivision of the SDRT dose, such that high-intensity vascular drivers of SDRT lethality, generated within a major tumor subvolume exposed to a high 24 Gy dose (high-dose planning target volume [PTV{sub HD]}), would equilibrate SDRT signaling intensity throughout the tumor interstitial space, rendering bystander radiosensitization of a minor subvolume (perfusion-modulated dose sculpting PTV [PTV{sub PMDS}]), dose-sculpted to meet a serial OAR dose/volume constraint. An engineered PTV{sub PMDS} may thus yield tumor ablation despite PMDS dose reduction and conformally avoiding OAR exposure to a toxic dose.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Application of FISH based G2-PCC assay for the cytogenetic assessment of high radiation dose exposures: Potential implications for rapid triage biodosimetry

The main goal of this study is to test the utility of calyculin A induced G2-PCC assay as a biodosimetry triage tool for assessing a wide range of low and acute high radiation dose exposures of photons. Towards this initiative, chromosome aberrations induced by low and high doses of x-rays were evaluated and characterized in G2-prematurely condensed chromosomes (G2-PCCs) by fluorescence in situ hybridization (FISH) using human centromere and telomere specific PNA (peptide nucleic acid) probes. A dose dependent increase in the frequency of dicentric chromosomes was observed in the G2-PCCs up to 20 Gy of x-rays. The combined yields of dicentrics and rings in the G2-PCCs showed a clear dose dependency up to 20 Gy from 0.02/cell for 0.1 Gy to 14.98/cell for 20 Gy. Centric rings were observed more frequently than acentric ring chromosomes in the G2-PCCs at all the radiation doses from 1 Gy to 20 Gy. A head-to-head comparison was also performed by FISH on the yields of chromosome aberrations induced by different doses of x-rays (0 Gy -7.5 Gy) in colcemid arrested metaphase chromosomes and calyculin A induced G2-PCCs. In general, the frequencies of dicentrics, rings and acentric fragments were slightly higher in G2-PCCs than in colcemid arrested metaphase chromosomes at all the radiation doses, but the differences were not statistically significant. To reduce the turnaround time for absorbed radiation dose estimation, attempt was made to obtain G2-PCCs by reducing the culture time to 36 hrs. The absorbed doses estimated in x-rays irradiated (0,1,2 and 4 Gy) G2-PCCs after 36 hrs of culture were grossly like that of G2-PCCs and colcemid arrested metaphase chromosomes prepared after 48 hrs of culture. Our study indicates that the shortened version of calyculin A induced G2-PCC assay coupled with the FISH staining technique can serve as an effective triage biodosimetry tool for large-scale radiological/nuclear incidents.

Science & Technology - Other Topics↗